Familial giant cell hepatitis associated with synthesis of 3 beta, 7 alpha-dihydroxy-and 3 beta,7 alpha, 12 alpha-trihydroxy-5-cholenoic acids

J Clin Invest. 1987 Apr;79(4):1031-8. doi: 10.1172/JCI112915.

Abstract

Urinary bile acids from a 3-mo-old boy with cholestatic jaundice were analyzed by ion exchange chromatography and gas chromatography-mass spectrometry (GC-MS). This suggested the presence of labile sulfated cholenoic acids with an allylic hydroxyl group, a conclusion supported by analysis using fast atom bombardment mass spectrometry (FAB-MS). The compounds detected by FAB-MS were separated by thin layer chromatography and high performance liquid chromatography. The sulfated bile acids could be solvolyzed in acidified tetrahydrofuran, and glycine conjugates were partially hydrolyzed by cholylglycine hydrolase. Following solvolysis, deconjugation, and methylation with diazomethane, the bile acids were identified by GC-MS of trimethylsilyl derivatives. The major bile acids in the urine were 3 beta,7 alpha-dihydroxy-5-cholenoic acid 3-sulfate, 3 beta,7 alpha,12 alpha-trihydroxy-5-cholenoic acid monosulfate, and their glycine conjugates. Chenodeoxycholic acid and cholic acid were undetectable in urine and plasma. The family pedigree suggested that abnormal bile acid synthesis was an autosomal recessive condition leading to cirrhosis in early childhood.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Hydroxysteroid Dehydrogenases / metabolism
  • Chenodeoxycholic Acid / analogs & derivatives*
  • Chenodeoxycholic Acid / biosynthesis
  • Chenodeoxycholic Acid / urine
  • Cholenes / biosynthesis*
  • Cholestasis / complications
  • Cholestasis / metabolism*
  • Cholic Acid
  • Cholic Acids / urine
  • Chromatography, Ion Exchange
  • Gas Chromatography-Mass Spectrometry
  • Hepatitis / complications
  • Hepatitis / genetics*
  • Hepatitis / metabolism
  • Humans
  • Infant, Newborn
  • Male
  • Spectrophotometry, Atomic

Substances

  • Cholenes
  • Cholic Acids
  • Chenodeoxycholic Acid
  • 3,7,12-trihydroxy-5-cholenoic acid
  • 3,7-dihydroxychol-5-enoic acid
  • 3-Hydroxysteroid Dehydrogenases
  • Cholic Acid